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DOI: 10.1055/s-0034-1367256
Treatment with low-dose flavonoids shows protective effects on endothelial cells
Objectives: Flavonoids are a large family of heterogeneous polyphenolic compounds found in fruits, vegetables and wine. Recent investigations revealed that flavonoids may be vascular protective agents by directly inducing nitric oxide (NO) production and arterial relaxation. This study aimed to investigate the protective effect of flavonoids on endothelial cell (EC) apoptosis and transendothelial migration of peripheral blood mononuclear cells (PBMCs) and to elucidate the potential mechanism affecting these processes.
Methods: EC were treated with different doses of the flavonoid Venoruton© (Novartis Pharma, Germany) to assess the potential effect on endothelial cell apoptosis by Annexin V and propidium iodide staining. EC monolayers were treated with Venoruton (0.1 mM, 0.5 mM, 1 mM) for 1 hour, and further used for transendothelial migration assay with human peripheral blood mononuclear cells (PBMCs). Results are expressed as percent of control (transmigration index, tmx). eNOS and iNOS expression in EC after Venoruton treatment were analyzed by RT-PCR.
Results: Venoruton exposure did not increase endothelial cell apoptosis. Treatment of EC with low-dose Venoruton© (0.1 mM, 0.5 mM) caused a significant decrease in transendothelial migration of PBMCs compared to control (control 1.00 ± 0.00 tmx vs. 0.1 mM 0.982 ± 0.004 tmx and 0.5 mM 0.983 ± 0.003 tmx). In contrast, high-dose Venoruton© (1 mM) treatment significantly increased transendothelial migration of PBMCs (control 1.00 ± 0.00 tmx vs. 1 mM 1.043 ± 0.016 tmx). eNOS as well as iNOS expressions were significantly elevated in EC with increasing Venoruton© dosage.
Conclusion: Low-dose Venoruton reduces apoptosis of endothelial cells and inhibit transendothelial migration of PMBCs trough endothelial monolayer, showing protective effects on ECs; however, high-dose Venoruton© inversely elevated transendothelial migration of PMBCs. The increased transendothelial migration of PBMCs is probably related to the excessive activation of the NO-axis and relaxation of the endothelial cells.